The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.

Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection.

Safety and immunogenicity of an inactivated eastern equine encephalitis virus vaccine.

Background: Eastern equine encephalitis virus (EEEV) is a mosquito borne alphavirus spread primarily in Atlantic and Gulf Coast regions of the United States. EEEV is the causative agent of a devastating meningoencephalitis syndrome, with approximately 30% mortality and significant morbidity. There is no licensed human vaccine against EEEV.

Intensive Care Unit-Like Care of Nonhuman Primates with Ebola Virus Disease.

Background: Ebola virus disease (EVD) supportive care strategies are largely guided by retrospective observational research. This study investigated the effect of EVD supportive care algorithms on duration of survival in a controlled nonhuman primate (NHP) model.

Methods: Fourteen rhesus macaques were challenged intramuscularly with a target dose of Ebola virus (1000 plaque-forming units; Kikwit).

The Western Equine Encephalitis Lyophilized, Inactivated Vaccine: An Update on Safety and Immunogenicity.

Background: Western Equine Encephalitis (WEE) is a naturally acquired infection and potentially devastating bioweapon, with no specific human countermeasures. An experimental inactivated Western Equine Encephalitis Vaccine (WEEV; WEE TSI-GSD 210) has been used under an IND (investigational New Drug) protocol at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 1976.

Methods: Over 24 years from 1987 to 2011, 876 subjects received 3 primary vaccine doses under 3 studies with 1,537 booster doses administered (FY87-8, phase 2, laboratory workers, vaccine lots 1-81-1, 1-81-2, and 2-1-91; FY99-12, phase 2 laboratory workers, lot 2-1-91; and FY09-02, phase 1 healthy volunteer, lot 3-1-92).

Pre-positioned Outbreak Research: The Joint Medical Emerging Diseases Intervention Clinical Capability Experience in Uganda.

The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens.

The Joint Mobile Emerging Disease Clinical Capability (JMEDICC) laboratory approach: Capabilities for high-consequence pathogen clinical research.

Following the 2013-2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC).

An Emerging Biothreat: Crimean-Congo Hemorrhagic Fever Virus in Southern and Western Asia.

Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in numerous countries, but the epidemiology and epizoology of Crimean-Congo hemorrhagic fever (CCHF) remain to be defined for most regions of the world. Using a broad database search approach, we reviewed the literature on CCHF and CCHFV in Southern and Western Asia to better define the disease burden in these areas. We used a One Health approach, moving beyond a focus solely on human disease burden to more comprehensively define this burden by reviewing CCHF case reports, human and animal CCHFV seroprevalence studies, and human and animal CCHFV isolations.

Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis.

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID).

Immune-Mediated Systemic Vasculitis as the Proposed Cause of Sudden-Onset Sensorineural Hearing Loss following Lassa Virus Exposure in Cynomolgus Macaques.

Lassa virus (LASV) causes a severe, often fatal hemorrhagic disease in regions in Africa where the disease is endemic, and approximately 30% of patients develop sudden-onset sensorineural hearing loss after recovering from acute disease. The causal mechanism of hearing loss in LASV-infected patients remains elusive. Here, we report findings after closely examining the chronic disease experienced by surviving macaques assigned to LASV exposure control groups in two different studies.

Ebola Virus Causes Intestinal Tract Architectural Disruption and Bacterial Invasion in Non-Human Primates.

In the 2014⁻2016 West Africa Ebola Virus (EBOV) outbreak, there was a significant concern raised about the potential for secondary bacterial infection originating from the gastrointestinal tract, which led to the empiric treatment of many patients with antibiotics. This retrospective pathology case series summarizes the gastrointestinal pathology observed in control animals in the rhesus EBOV-Kikwit intramuscular 1000 plaque forming unit infection model. All 31 Non-human primates (NHPs) exhibited lymphoid depletion of gut-associated lymphoid tissue (GALT) but the severity and the specific location of the depletion varied.

Persistent Marburg Virus Infection in the Testes of Nonhuman Primate Survivors.

Sexual transmission of filoviruses was first reported in 1968 after an outbreak of Marburg virus (MARV) disease and recently caused flare-ups of Ebola virus disease in the 2013-2016 outbreak. How filoviruses establish testicular persistence and are shed in semen remain unknown. We discovered that persistent MARV infection of seminiferous tubules, an immune-privileged site that harbors sperm production, is a relatively common event in crab-eating macaques that survived infection after antiviral treatment.

Distinguishing Respiratory Features of Category A/B Potential Bioterrorism Agents from Community-Acquired Pneumonia.

Differentiating between illness caused by community-acquired respiratory pathogens versus infection by biothreat agents is a challenge. This review highlights respiratory and clinical features of category A and B potential biothreat agents that have respiratory features as their primary presenting signs and symptoms. Recent world events make such a reminder that the possibility of rare diseases and unlikely events can occur timely for clinicians, policymakers, and public health authorities.

Treatment-focused Ebola trials, supportive care and future of filovirus care.

During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients.

Clinical Laboratory Values as Early Indicators of Ebola Virus Infection in Nonhuman Primates.

The Ebola virus (EBOV) outbreak in West Africa during 2013-2016 demonstrated the need to improve Ebola virus disease (EVD) diagnostics and standards of care. This retrospective study compared laboratory values and clinical features of 3 nonhuman primate models of lethal EVD to assess associations with improved survival time. In addition, the study identified laboratory values useful as predictors of survival, surrogates for EBOV viral loads, and triggers for initiation of therapeutic interventions in these nonhuman primate models.

Will There Be a Cure for Ebola?

Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk-pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid-based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp).

Activity of Norspermidine on Bacterial Biofilms of Multidrug-Resistant Clinical Isolates Associated with Persistent Extremity Wound Infections.

Biofilm formation is a major virulence factor for numerous pathogenic bacteria and is cited as a central event in the pathogenesis of chronic human infections, which is in large part due to excessive extracellular matrix secretion and metabolic changes that occur within the biofilm rendering them highly tolerant to antimicrobial treatments. Polyamines, including norspermidine, play central roles in bacterial biofilm development, but have also recently been shown to inhibit biofilm formation in select strains of various pathogenic bacteria. The aim of this study was to evaluate in vitro the biofilm dispersive and inhibitory activities of norspermidine against multidrug-resistant clinical isolates of Acinetobacter baumannii(n = 4), Klebsiella pneumoniae (n = 3), Pseudomonas aeruginosa (n = 5) and Staphylococcus aureus (n = 4) associated with chronic extremity wound infections using the semi-quantitative 96-well plate method and confocal laser microscopy.

Deployment of the 1st Area Medical Laboratory in a Split-Based Configuration During the Largest Ebola Outbreak in History.

Background: The U.S. Army 1 Area Medical Laboratory (1 AML) is currently the only deployable medical CBRNE (Chemical, Biological, Radiological, Nuclear, and Explosives) laboratory in the Army's Forces Command.

Antiviral therapeutics for the treatment of Ebola virus infection.

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials.

Optimization of time to initial vancomycin target trough improves clinical outcomes.

Background: Outcomes data for the efficacy of interventions designed to decrease the time to initial target vancomycin troughs are sparse.

Objective: A vancomycin therapeutic drug monitoring (TDM) program was initiated to reduce the time to initial target troughs and to examine the impact on clinical outcomes.

Methods: Single-center, pre- and post-intervention observational study in a 250 bed teaching facility.

Monitoring Exposure to Ebola and Health of U.S. Military Personnel Deployed in Support of Ebola Control Efforts - Liberia, October 25, 2014-February 27, 2015.

In response to the unprecedented Ebola virus disease (Ebola) outbreak in West Africa, the U.S. government deployed approximately 2,500 military personnel to support the government of Liberia.

Operation United Assistance: infectious disease threats to deployed military personnel.

As part of the international response to control the recent Ebola outbreak in West Africa, the Department of Defense has deployed military personnel to train Liberians to manage the disease and build treatment units and a hospital for health care volunteers. These steps have assisted in providing a robust medical system and augment Ebola diagnostic capability within the affected nations. In order to prepare for the deployment of U.